The degree of behavioral control which an organism has over a stressor (ability to alter the onset, termination, duration, intensity, or temporal pattern of the event) is an important determinant of the behavioral and physiological impact of the stressor. Numerous behavioral, neurochemical, hormonal, and immunological changes follow exposure to a stressor if it is uncontrollable, but not if the identical stressor is controllable. Effects such as these which depend on the uncontrollability of a stressor have been called "learned helplessness effects". They have played an important role in psychological theory, in understanding the physiology of stress, in understanding the environmental regulation of endogenous pain modulation mechanisms and immune function, and have been proposed to be involved in the etiology of numerous human disorders. Depression, anxiety disorders, and post- traumatic stress disorder are but examples. Despite the seeming importance of stressor controllability and the considerable amount of research that has been directed at explaining its operation, there is still no adequate general explanation at either the behavioral or physiological level. The present proposal develops an integrated behavioral and physiological explanation of learned helplessness effects. It also gives special attention to an exploration of the proximate causes of the behavioral changes at the time of test. At a behavioral level the critical issue to be tested is whether uncontrollable stressors might produce intense "anxiety" that dissipates over a 3-5 day period, and whether some of all of the behavioral sequelae of IS might reflect this state of anxiety. At a physiological level the proposed research will explore the possibility that this state of anxiety involves a temporarily hyper-responsive serotonergic (5-HT) system originating from the dorsal raphe nucleus (DRN). The proposed research will also determine the cause of this hyper-responsivity, with a focus being on GABAergic mechanisms. Finally it will explore whether the diverse behavioral outcomes of exposure to uncontrollable stressors are produced by the 5-HT projections of the DRN.